Abstract
The role of DNA methylation of breast cancer-infiltrating immune cells has not been fully explored. We conducted a cohort-based retrospective study analyzing the genome-wide immune-related DNA methylation of 1057 breast cancer patients from the TCGA cohort and GSE72308 cohort. Based on patients’ overall survival (OS), a prognostic risk score system using 18 immune-related methylation genes (IRMGs) was established and further validated in an independent cohort. Kaplan–Meier analysis showed a clear separation of OS between the low- and high-risk groups. Patients in the low-risk group had a higher immune score and stromal score compared with the high-risk group. Moreover, the characteristics based on 18-IRMGs signature were related to the tumor immune microenvironment and affected the abundance of tumor-infiltrating immune cells. Consistently, the 18-IRMGs signatures showed similar influences on immune modulation and survival in another external validation cohort (GSE72308). In conclusion, the proposed 18-IRMGs signature could be a potential marker for breast cancer prognostication.
Highlights
The biological behavior and clinical outcome of breast cancer are highly heterogeneous [1, 2]
To explore the pattern of immune infiltration based on DNA methylation in breast cancer, we first compiled the The Cancer Genome Atlas (TCGA) methylation profile and GSE72308 methylation profile (Figure 1) to identify the corresponding immune-related methylation genes (IRMGs)
We analyzed the relationship between DNA methylation and tumor immunity of breast cancer through the IRGMs set, and identified two immune methylation clusters significantly related to patient survival, which was validated in an independent cohort
Summary
The biological behavior and clinical outcome of breast cancer are highly heterogeneous [1, 2]. The tumor microenvironment is a complex mixture of malignant and non-malignant cells including immune cells which can affect the behavior and clinical outcomes of breast cancer. Singlecell RNA sequencing of breast cancer has confirmed that there is a complex mixture of immune T cell subtypes in tumors [6, 7]. DNA methylation, RNA and protein levels can be used as prognostic markers [12]. These markers have their own advantages and disadvantages. DNA methylation and RNA sequencing results can be obtained by high-throughput chip or sequencing [13], which is more efficient and economical. Few studies have explored the impact of immune cell infiltration on cancer from the perspective of DNA methylation patterns
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